It is known that carnitine (also known as .beta.-hydroxy-.gamma.-trimethylaminobutyric acid) has a center of asymmetry in the .beta. position and, therefore, two stereoisomers may exist. The stereoisomers are referred to as the D and L forms, antipodes, or optical enantiomers.
L(-)-carnitine chloride has an important role in human metabolism, particularly in the transfer of fatty acids. D(+)-carnitine, on the other hand, is an inhibiting agent which competes with L(-)-carnitine for the enzyme L(-)-carnintineacyltransferase, possibly resulting in lowering the level of L(-)-carnitine present in cardiac tissue. Fritz, I. B., Schultz, S. K, J. Biol. Chem. (1965) 240 2188; Roe, C. R., Bohan, T. P., Lancet (1982) 1411.
The commonly known therapeutic uses of L(-)-carnitine are as an eutrophyic agent and as a cardioprotecting agent in the treatment of myocardial ischemias, angina pectoris and schlerois of the myocardium.
There are processes known for synthesizing carnitine. Most of the known processes, however, result in the production of carnitine in both the D and L forms. Thus, an additional step is required for separating the racemic mixture into its two optical enantiomers. These known processes require expensive reactants which are optically active such as, for example, dibenzoyltartaric acid, camphoric acid, mandelic acid, and the like. Additionally, the reaction conditions must be carefully controlled. Also, several crystallization steps are necessary. Consequently, known processes for synthesizing L(-)-carnitine are generally economically burdensome and thus impractical for industrial application. (See European Patent Application EP 141,408; French Patent 1,466,696 and British Patent G.B. - A - 2,131,049.)
There is also described a process for synthesizing L(-)-carnitine from an optically active compound such as D-mannitol (see European Patent Application EP 60,595). While this process does not require separation of D and L enantiomers, the synthesis is complex in that a large number of individual steps must be performed. Moreover, expensive and potentially dangerous reactants such as lead tetraacetate are used in the process.
Some microbiological processes for preparing L(-)-carnitine from prochiralic substrates, such as alkyl chloroacetoacetates, crotonobetaines or butyrobetaines are also known (see Belgian Patent BE 898,396; European Patent Application EP 122,794; French Patent Application FR 2,485,564). Such processes have the disadvantages of requiring bulky reaction volumes, resulting in low yields, and difficulty in purifying the products.
Therefore, there is a need for a simple, efficient and economical process for preparing L(-)-carnitine on an industrial scale.
The present invention provides a method for the preparation of L(-)-carnitine chloride which is simple to perform and advantageous from an industrial standpoint.